Gamma-hydroxybutyrate compositions having improved pharmacokinetics in the fed state
Oral pharmaceutical compositions of sodium oxybate having improved pharmacokinetic properties when administered less than two hours after eating are provided, and therapeutic uses thereof.
1. A method of decreasing excessive daytime sleepiness in a human subject, the method comprising:
orally administering a pharmaceutical composition comprising calcium oxybate, magnesium oxybate, and potassium oxybate,
wherein the orally administering occurs only once nightly at least two hours after eating.
2. The method of claim 1 , wherein the pharmaceutical composition comprises calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate.
3. The method of claim 1 , wherein orally administering achieves a mean AUCinf of about 273 hr*μg/mL when administration is about 2 hours after eating.
4. The method of claim 1 , wherein orally administering achieves a tmax of greater than 1 hour.
5. The method of claim 1 , wherein orally administering is effective to induce sleep for at least six consecutive hours.
6. The method of claim 1 , wherein orally administering is effective to induce sleep for at least eight consecutive hours.
7. The method of claim 1 , wherein the human subject achieves a decrease in excessive daytime sleepiness when measured by the Epworth Sleepiness Scale (ESS).
8. The method of claim 1 , wherein the human subject achieves a decrease in excessive daytime sleepiness when measured by the Maintenance of Wakefulness Test.
9. The method of claim 1 , wherein the human subject achieves an improved Clinical Global Impression (CGI) rating of sleepiness.
10. The method of claim 1 , wherein the human subject achieves a decrease in weekly cataplexy attacks.
11. The method of claim 1 , comprising mixing the pharmaceutical composition with water prior to orally administering.
12. The method of claim 1 , wherein the pharmaceutical composition comprises a powder.
13. The method of claim 1 , wherein the pharmaceutical composition comprises viscosifying or suspending agents.
14. The method of claim 1 , wherein the pharmaceutical composition comprises an immediate release portion.
15. The method of claim 14 , wherein the immediate release portion releases at least 80% of its gamma-hydroxybutyrate salt in 1 hour when tested in a dissolution apparatus 2 according to USP 38<711> in a 0.1 N HCl dissolution medium at a temperature of 37° C. and a paddle speed of 75 rpm.
16. The method of claim 1 , wherein the pharmaceutical composition comprises an immediate release portion and modified release portion.
17. The method of claim 16 , wherein the immediate release portion comprises calcium oxybate, magnesium oxybate, and potassium oxybate.
18. The method of claim 16 , wherein the modified release portion comprises sodium oxybate.
19. The method of claim 1 , wherein the pharmaceutical composition comprises crystals or spheres.
20. The method of claim 19 , wherein the crystals or spheres comprise lactose, sucrose, or microcrystalline cellulose.
21. The method of claim 1 , wherein the pharmaceutical composition comprises spheres or granules.
22. The method of claim 21 , wherein the spheres comprising sucrose.
23. The method of claim 21 , wherein the spheres comprise maltodextrin.